fa بررسی آزمایشگاهی اثرات سمیت سینرژیک Sophoraflavanone G استخراج شده از Sophora pachycarpa و داروی سیس پلاتین و دوستاکسل بر روی کارسینومای سلول سنگفرشی حفره دهان بیوتکنولوژی Biotechnology پژوهشي اصیل Original Research <span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">زمینه و هدف</span></span></b><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">: کارسینوم سلول سنگفرشی حفره دهان شایع‌ترین نئوپلاسم سرطان‌های سر و گردن است که بیش از 90 درصد از تمام سرطان‌های حفره دهان را شامل می‌شود. نشان داده شده است که ترکیبات طبیعی اثرات ضدسرطانی قابل توجهی برروی سلول‌های بدخیم دارند. از این میان، </span></span><i><span dir="LTR" style="font-family:" times="">Sophora pachycarpa</span></i><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar=""> یکی از منابع ترکیبات</span></span> <span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">فلاونوئیدی مانند </span></span><span dir="LTR" style="font-family:" times="">sophoraflavanone G</span><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar=""> (</span></span><span dir="LTR" style="font-family:" times="">SG</span><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">) است که دارای طیف وسیعی از خواص</span></span> <span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">بیولوژیکی از جمله اثرات ضدسرطانی است. بنابراین، این مطالعه به منظور بررسی اثرات سیتوتوکسیک </span></span><span dir="LTR" style="font-family:" times="">SG</span><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar=""> استخراج شده از </span></span><i><span dir="LTR" style="font-family:" times="">S. pachycarpa</span></i><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar=""> در ترکیب با داروی سیس‌پلاتین و یا دوستاکسل بر روی</span></span> <span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">سلول‌های کارسینومای سلول سنگفرشی حفره دهان (سلول‌های </span></span><span dir="LTR" style="font-family:" times="">KB</span><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">) در شرایط برون‌تنی طراحی و انجام شد.</span></span><span dir="LTR" style="font-family:"Times",serif"></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">مواد و روش‌ها</span></span></b><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">: برای انجام این کار، </span></span><span dir="LTR" style="font-family:" times="">SG</span><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar=""> از </span></span><i><span dir="LTR" style="font-family:" times="">S. pachycarpa</span></i><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar=""> با خلوص بیش از 95 درصد</span></span> <span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">استخراج شد. برای تعیین اثرات سیتوتوکسیک داروها از روش </span></span><span dir="LTR" style="font-family:" times="">MTT</span><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar=""> استفاده شد. برای بررسی اثرات</span></span> <span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">ترکیبی </span></span><span dir="LTR" style="font-family:" times="">SG</span><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar=""> و سیس‌پلاتین و یا دوستاکسل بر روی سلول‌های </span></span><span dir="LTR" style="font-family:" times="">KB</span><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">، شاخص ترکیبی (</span></span><span dir="LTR" style="font-family:" times="">CI</span><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">) داروها از طریق نرم افزار</span></span> <span dir="LTR" style="font-family:" times="">CompuSyn</span><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar=""> مورد ارزیابی قرار گرفت</span></span><span dir="LTR" style="font-family:" times="">.</span><span lang="FA" style="font-size:12.0pt"><span style="font-family:"B Zar""></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">یافته‌ها</span></span></b><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">: نتایج نشان داد که </span></span><span dir="LTR" style="font-family:" times="">SG</span><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar=""> اثرات سیتوتوکسیک قابل توجهی برروی سلول‌های </span></span><span dir="LTR" style="font-family:" times="">KB</span><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar=""> در مقایسه با </span></span><span dir="LTR" style="font-family:" times="">HEK-293</span><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar=""> دارد. برخلاف سلول‌های نرمال، این ترکیب فعالیت ضدسرطانی سیس‌پلاتین/دوستاکسل را در برابر سلول‌های </span></span><span dir="LTR" style="font-family:" times="">KB</span><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar=""> افزایش داد. </span></span>&nbsp;<span dir="LTR" style="font-family:" times="">SG</span><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">و سیس‌پلاتین/دوستاکسل در غلظت‌های ترکیبی پایین، اثرات هم‌افزایی قابل قبولی</span></span> <span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">بر روی سلول‌های </span></span><span dir="LTR" style="font-family:" times="">KB</span><span style="font-size:12.0pt"><span b="" style="font-family:" zar=""> با شاخص ترکیبی بین 0.33-0.43 ایجاد کردند. در کنار آن، ترکیب دارو و ماده تغییرات مورفولوژیکی قابل توجهی ایجاد کرد که احتمالا می‌توان آن را به عنوان</span></span> <span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">شاخص آپوپتوز در نظر گرفت.</span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">نتیجه‌گیری</span></span></b><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">: در مجموع، </span></span><span dir="LTR" style="font-family:" times="">SG</span><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar=""> می‌تواند کاندید مناسبی برای درمان هدفمند سرطان دهان معرفی شود. </span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span lang="AR-SA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">کلمات کلیدی</span></span></b><span lang="AR-SA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">: </span></span><i><span dir="LTR" style="font-family:" times="">Sophora pachycarpa</span></i><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">، </span></span><span dir="LTR" style="font-family:" times="">Sophoraflavanone G</span><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">، سیس‌پلاتین، دوستاکسل، کارسینوم سلول سنگفرشی حفره دهان، رده سلولی </span></span><span dir="LTR" style="font-family:" times="">KB</span><span lang="FA" style="font-size:12.0pt"><span b="" style="font-family:" zar="">، سمیت سلولی، اثرات ترکیبی</span></span><span dir="LTR" style="font-family:"Times",serif"></span></span></span></span></span></span><br> &nbsp; <span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Background and Aim</span></span></b><span new="" roman="" style="font-family:" times="">: </span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Oral squamous cell carcinoma is the most common neoplasm form in the oral cavity comprising 90% of all oral cavity cancers. It has been shown that natural compounds could exert significant anti-cancer effects on malignant cells. Amongst, </span></span><i><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Sophora pachycarpa</span></span></i><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">, one of the sources of flavonoid compounds such as sophoraflavanone G (SG</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">), </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">possesses wide range of biological properties including anticancer effects. Therefore, this study was performed to investigate the cytotoxic effects of SG extracted from <i>S. pachycarpa</i> in combination with cisplatin/docetaxel on </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">oral squamous cell carcinoma</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> cells. </span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Materials and Methods</span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> : </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">To do so, SG was extracted from <i>S. pachycarpa</i> with more than 95% purity. The MTT assay was used to determine the cytotoxic effects of the drugs. To investigate the combinational effects of SG and drugs on KB cells, combination index (CI) was evaluated through the CompuSyn software.</span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Results</span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">: </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">The results showed that SG exhibited considerable cytotoxic effects on KB cells compared to HEK-293 cells. Despite normal cells, this compound enhanced anticancer activity of cisplatin/docetaxel against KB cells. The combination index showed that SG and cisplatin/docetaxel in low combinational concentrations produced synergistic cytotoxic effects on KB cells with a combination index values between 0.3-0.4. Alongside, SG+cisPt/DTX caused noticeable morphological changes that could be consider as an apoptotic indicator. </span></span><span lang="X-NONE" style="font-size:12.0pt"><span style="font-family:"Times New Roman",serif"></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Conclusion</span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">: </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">These results suggested the potency of SG to enhance the anticancer activity of cisplatin/docetaxel on KB cell lines. While, it reduces the cytotoxic effects of cisPt/DTX on HEK-29 cells. Therefore, SG could be introduced as a promising candidate for </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">the targeted treatment of oral cancer.</span></span><span dir="RTL" lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"Times New Roman",serif"></span></span></span></span></span><br> &nbsp; Sophora pachycarpa, Sophoraflavanone G, سیس پلاتین, دوستاکسل, کارسینوم سلول سنگفرشی حفره دهان, اثرات ترکیبی, رده سلولی KB, سمیت سلولی Sophora pachycarpa, Sophoraflavanone G, Cisplatin, Docetaxel, Squamous cell carcinoma, KB cell line, cytotoxicity, combinational effects, KB cell line, cell cytotoxicity 33 43 http://sjku.muk.ac.ir/browse.php?a_code=A-10-7902-1&slc_lang=fa&sid=1 Manouchehr Teymouri منوچهر تیموری manochehr.teimory@gmail.com 5400319475328460072208 5400319475328460072208 No Negar Abdolahzadeh نگار عبدالله زاده abdolahzadeh.negar@gmail.com 5400319475328460072209 5400319475328460072209 No Saied Mahmoodi سعید محمودی saidmahmoodi2020@gmail.com 5400319475328460072210 0009-0001-3479-6713 No Fatemeh Didari Meymand فاطمه دیداری میمند fatemehdidari2015@gmail.com 5400319475328460072211 0009-0003-4285-0070 No Milad Iranshahi میلاد ایرانشاهی Iranshahym@mums.ac.ir 5400319475328460072212 5400319475328460072212 No Javid Rasekhi جاوید راسخی J.Rasekhi@nkums.ac.ir 5400319475328460072213 5400319475328460072213 No Mahla Abdari مهلا آبداری mahla_abdari@yahoo.com 5400319475328460072214 0009-0003-2837-0716 No Alireza Afshari-Safavi علیرضا افشاری صفوی alireza.afsharisafavi@gmail.com 5400319475328460072215 5400319475328460072215 No Javad Hashemi جواد هاشمی J.hashemi@nkums.ac.ir 5400319475328460072216 5400319475328460072216 No Fahimeh Khaghani فهیمه خاقانی F.khaghani@nkums.ac.ir 5400319475328460072217 0009-0000-6128-8691 No Samaneh Mollazadeh سمانه ملازاده samanehmollazadeh@yahoo.com 5400319475328460072218 5400319475328460072218 Yes